Methods, systems, and devices for monitoring anisocoria and asymmetry of pupillary reaction to stimulus

ABSTRACT

A computer program is disclosed for performing the following method: recording images of a response of a left pupil to a stimulus thereby resulting in a first set of sequential images; recording images of a response of a right pupil to the same stimulus at the same time as the first images were recorded, thereby resulting in a second set of sequential images; displaying on a display simultaneously the first set of images and the second set of image, wherein the two sets of images are synchronized, and wherein a center of the left pupil of each image from the first set of sequential images is aligned with a center of the right pupil from the second set of sequential images on the display.

PRIORITY

This is a continuation of U.S. patent application Ser. No. 13/929,795,filed Jun. 28, 2013, which is a continuation of U.S. patent applicationSer. No. 13/149,926, filed Jun. 1, 2012, now U.S. Pat. No. 8,534,840,which is a continuation of U.S. patent application Ser. No. 12/626,452,filed Nov. 25, 2009, now U.S. Pat. No. 7,967,442, which claims priorityfrom U.S. Provisional Patent Application Ser. No. 61/118,541, filed onNov. 28, 2008, the entire disclosures of which are incorporated byreference herein.

TECHNICAL FIELD OF THE DISCLOSURE

The present disclosure relates to methods, systems and devices orinstruments for monitoring anisocoria and asymmetry of reaction tostimulus between the left and right pupil of a subject, sometimesreferred to herein as a “patient” or an “individual”. The methods andsystems can be implemented through devices and instruments such asPupillometers, which are high-tech instruments that are currently usedto obtain information about a pupil's response to a stimulus. Examplesof such Pupillometers are described in detail in U.S. Pat. Nos.6,116,736, 6,260,968, 6,820,979, and 7,147,327, all of which areincorporated herein by reference in their entirety. Examples ofPupillometers in commercial use include the ForeSite™ Pupillometer, theNPi-™ 100 Pupillometer, the PLR-100™ Pupillometer, the DP1000™Pupillometer, and the A-1000™ Pupillometer, all made by Neuroptics®, andall incorporated herein by reference in their entirety. These types ofpupillometers can be used on human or animal subjects.

BACKGROUND OF THE DISCLOSURE

Systems for monitoring pupil size and pupil responsivenesscharacteristics are well known in the art and are generally referred toas pupillometry systems or, simply, pupillometers. One earlyPupillometer is described in U.S. Pat. No. 3,533,683, which issued toStark et al. on Oct. 13, 1970 and is entitled “Dynamic PupillometersUsing Television Camera System” (incorporated herein by reference). TheStark et al. system employed a television camera system, a digitalcomputer system, an infrared light source, and a visual light stimulatorfor determining the instantaneous size of a pupil as an eye (orneurologic pupilary control system) of a patient was exposed to variousstimuli.

More advanced hand-held pupillometers are now commercially available andcan be used in many applications including critical care,anesthesiology, research, and refractive surgery and ophthalmology. Oneexample is the PLR-100™ Pupillometer by Neuroptics®. The PLR-100™pupillometer is a hand-held and cordless device which measures pupilsize and dynamics. It can be used for either a static pupil measurementprotocol (i.e., reporting pupil size measurements such as weightedaverage pupil size and standard deviation) as well as a dynamic pupilmeasurement protocol (i.e., reporting pupil light reflex measurementsincluding: maximum pupil size before constriction, minimum pupil sizeafter constriction, percent constriction, average constriction velocity,maximum constriction velocity, dilation velocity and time to reach 75%of the initial maximum pupil size after the constriction). The user canadjust the light stimulus intensity and duration. Numerical results aredisplayed on a color LCD numerically and graphically. Measurements mayalso be printed to a portable printer via infrared (wirelessly)transmission.

One area of pupillary clinical diagnosis and monitoring that has gainedincreased attention over the years is detecting and monitoringdifferences in size and asymmetry in pupillary response to stimulusbetween the left and right pupils. This condition where the sizes of theleft and right pupils of an individual at rest are unequal is calledanisocoria. A variety of potential causes for anisocoria exist, rangingfrom trivial or normal variation, to life threatening conditions, suchas increased intracranial pressure (ICP) and brain swelling from a headinjury, uncal herniation, lesions, and aneurismal compression. Ingeneral all those neurological conditions affecting the efferent pathwayof the pupil system starting from the oculomotor nuclei in the midbrainup to the pupil sphincter muscle can be a cause of anisocoria.

Asymmetry in pupillary response is when the left and right pupilsrespond to a stimulus, such as a light stimulus, in different ways thatgo beyond the definition of anisocoria. For example, the pupil sizebetween the left and right pupils at rest may be the same or very closein size, but the two pupils may react to a stimulus very differently,such as having different maximum pupil size before constriction, minimumpupil size after constriction, percent constriction, averageconstriction velocity, maximum constriction velocity, dilation velocityand time to reach 75% of the initial maximum pupil size after theconstriction. Like anisocoria, asymmetry in pupillary response may alsobe indicative of an underlying medical condition.

Because anisocoria and asymmetry in pupilary response may be symptoms insome cases of very serious and immediately life threatening conditions,it is important for medical practitioners to have tools for easy, quickand convenient ways to accurately detect, measure, and view in real-timedifferences in pupilary size and pupilary reaction to stimulus betweenthe right and left pupils. There are, unfortunately, very few such toolspresently available. Thus, there is a need for high-tech instrumentsthat can perform such functions. The methods, systems and devices of thepresent disclosure meet this and other such needs in the art.

SUMMARY OF THE DISCLOSURE

In one embodiment, a Pupillometer is disclosed. The Pupillometer has adisplay, an imaging apparatus that has a pupil finder and amicroprocessor, and a memory in communication with the microprocessor.The display is sized to simultaneously display a video of y or moreseconds in length of a left pupil and a video of y or more seconds inlength of a right pupil. The pupil finder identifies the perimeter of apupil. The imaging apparatus is capable of recording images of anindividual's pupils at a rate of x image frames per second for a periodof y or more seconds and playing back said image frames as a video at ximage frames per second or at another rate that is faster or slower thanx image frames per second. The memory has stored therein a program forenabling said microprocessor to do the following: (i) identify a centerof the left pupil and a center of the right pupil for each image frame;(ii) synchronize each image frame of the two videos starting from thefirst frame; (iii) cause the display to display the two videossimultaneously such that each of the image frames of the video of theleft eye is synchronized to a corresponding image frame of the video ofthe right eye when played back on the display; and (iv) cause the twovideos to be displayed so that the center of the left pupil in eachimage frame is aligned on the display with the center of the right pupilfor the corresponding image frame.

In another embodiment, a method for monitoring asymmetry in response toa stimulus between a left pupil and a right pupil of an individual isdisclosed. The method includes the following steps: recording for aperiod of time y at a rate of x image frames per second a response of aleft pupil to the stimulus thereby resulting in a first set ofsequential image frames; recording for the same period of time y at thesame rate of x image frames per second a response of a right pupil tothe stimulus thereby resulting in a second set of sequential imageframes; and displaying on a display simultaneously the first set ofimage frames of the response of the left pupil to the stimulus and thesecond set of image frames of the response of the right pupil to thestimulus. The two sets of image frames are synchronized per framestarting from the first frame for each set, and a center of the leftpupil is aligned with a center of the right pupil on the display.

In another embodiment, a program product comprising a computer-readablemedium and computer-executable instructions recorded on thecomputer-readable medium for performing a method is disclosed. Themethod comprises: recording for a period of time y at a rate of x imageframes per second a response of a left pupil to the stimulus therebyresulting in a first set of sequential image frames; recording for thesame period of time y at the same rate of x image frames per second aresponse of a right pupil to the stimulus thereby resulting in a secondset of sequential image frames; displaying on a display simultaneouslythe first set of image frames of the response of the left pupil to thestimulus and the second set of image frames of the response of the rightpupil to the stimulus. The two digital sets of image frames aresynchronized per frame starting from the first frame for each set, and acenter of the left pupil is aligned with a center of the right pupil onthe display.

Other features and advantages will be apparent from the followingdescription of the various embodiments of the disclosure, whichillustrate, by way of example, the principles of the disclosed devicesand methods.

BRIEF DESCRIPTION OF THE DRAWINGS

According to common practice, the various features of the drawings maynot be presented to scale. Rather, the dimensions of the variousfeatures may be arbitrarily expanded or reduced for clarity. Included inthe drawings are the following figures:

FIG. 1 is an illustration of a Pupillometer having a display inaccordance with one embodiment.

FIG. 2 is an illustration of the Pupillometer depicted in Figure onebeing used to take a measurement of the pupil of a right eye of anindividual in response to a visual light stimulus.

FIG. 3 shows a screen shot of the display of the Pupillometer depictedin FIG. 1 showing results of a measurement of a pupil of an individualin response to a visual light stimulus.

FIGS. 4A-4C depict the steps taken by the handler of the Pupillometerdepicted in FIG. 1 in order to take pupilary measurements.

FIG. 5 shows a screen shot of the display of the Pupillometer depictedin FIG. 1 showing the left and right pupils of an individual alignedduring video playback of pupilary response to a light stimulus.

FIG. 6 shows second screen shot from the same video described withrespect to FIG. 5.

FIGS. 7-9 show different screen shots of the display of the Pupillometerdepicted in FIG. 1 showing the left and right pupils of an individualaligned during video playback of pupilary response to a light stimulusalong with a graphical representation of the pupilary response.

DETAILED DESCRIPTION

Disclosed herein is a pupillary analysis system that includes apupillometer, such as the one shown in FIG. 1, with features that enableit to monitor and compare in real-time the response of an individual'sleft and right pupils to a stimulus, such as a light stimulus, auditorystimulus, or noxious stimulus. In the examples described herein thepupillometer has a light stimulus source built into it. Variations onthe type of stimulus and the arrangement of that stimulus in relation tothe pupillometer, such as those variations described in U.S. Pat. No.7,147,327, are also contemplated and incorporated herein by reference.The working components, electronics, and software, other than thosedescribed below, are also fully described in, e.g., U.S. Pat. No.7,147,327, and will therefore not be further discussed herein.

Before the present subject matter is further described, it is to beunderstood that the subject matter described herein is not limited tothe particular embodiments described, and as such may of course vary. Itis also to be understood that the terminology used here in is for thepurpose of describing particular exemplary embodiments only, and is notintended to be limiting in any fashion, and in particular to thedoctrine of equivalents. Unless defined otherwise, all technical termsused herein have the same meaning as commonly understood by one skilledin the art to which this subject matter belongs.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit, unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range, and any other stated or intervening value in thatstated range, is encompassed within the subject matter described herein.The upper and lower limits of these smaller ranges may independently beincluded in the smaller ranges, and are also encompassed within thesubject matter described herein, subject to any specifically excludedlimit in the stated range. Where the stated range includes one or bothof the limits, ranges excluding either or both of those included limitsare also included in the subject matter described herein.

It must be noted that as used herein and in the appended claims, thesingular forms “a,” “and,” and “the” include plural referents unless thecontext clearly dictates otherwise.

FIG. 1 depicts a handheld pupillometer, such as that described in U.S.Pat. No. 7,147,327. Pupillometer 10 includes a display 12, handle 15 forgripping the pupillometer while using it, and headrest 16. Headrest 16is used to position the pupillometer 10 optimally to take measurementsof the pupils of an individual's eyes. U.S. Pat. No. 7,216,985, which isincorporated herein by reference in its entirety, describes headrests ofthe type that may be used with pupillometer 10. Pupillometer 10 alsoincludes a keypad 14, including various control buttons includingbuttons 14 a and 14 b, which are used to operate the pupillometer 10.

Pupillometer 10 operates essentially as a handheld optical scanner. Inone embodiment, it stimulates the eye of an individual with a flash oflight and captures and analyzes a rapid sequence of digital images toobtain a temporal measurement of the diameter of the individual's pupil.The intensity and duration of the light stimulus can be set by the userof pupillometer 10 using the controls in the keypad 14. In oneembodiment, maximum light strength is approximately 180 μW and maximumduration is approximately 800 ms. Pupillometer 10 can acquire imagesusing a self-contained infrared illumination source and a digitalcamera. It analyzes the captured image data and displays a summary ofthe measurement in the display 12, which can be an LCD display. Data mayalso be printed out on an optional thermal printer or downloaded to anexternal computer via an infrared port (IrDA) or transmitted via USBport and cable to a computer. Pupillometer 10 can use a menu drivengraphical user interface with a color LCD screen 12 for data display. Akeypad 14 completes the user interface and enables manual entry ofindividual subject identification (ID) numbers and other information.

Pupillometer 10 can be powered by any number of power sources known tothose of skill in the art. In one embodiment it is powered by a 4.2 voltrechargeable lithium ion battery.

Pupillary data sampled at approximately ten frames per second (10fps)(or less), approximately twenty frames per second (20 fps),approximately thirty frames per second (30 fps), approximately fortyframes per second (40 fps), approximately fifty frames per second (50fps), or more and for a total duration of up to about 3600 seconds(i.e., about 60 minutes) can be used in the calculation of a number ofdifferent pupillary reaction variables that can be displayed numericallyor graphically on the display 12 at the end of each measurement. In oneembodiment, the Pupillometer 10 takes one measurement of a pupil bysampling thirty frames per second (30 fps) for three seconds to acquirea total of approximately ninety sequential images of a pupil's responseto a stimulus. Pupillometer 10 can sample data at anywhere between about1 frame per second (1 fps) (or less) to about one hundred frames persecond (100 fps) (or more) for any length of time between about one (1)second (or less) and about 3600 seconds (i.e., about 60 minutes).

Pupillometer 10 has internal memory large enough to store three hundredor more measurements. All measurement data contained in Pupillometer's10 memory can be downloaded to an external computer or laptop, such as aWindow® based computer or laptop or computer or laptop with a differentoperating system. Measurement data can be encrypted and contained in afile named with the date and time of the moment of the download andextention “dat”. For example, R_20080909_1030.dat would indicate a filedownloaded on Sep. 9, 2008 at 10:30. Previous measurements and data canbe browsed, retrieved and printed using the keypad controls 14 andappropriate menus displayed in the screen display 12.

FIG. 2 shows pupillometer 10 being used to take a measurement of thepupil of a right eye of an individual in response to a visual lightstimulus. As shown, the operator of pupillometer 10 positionspupillometer 10 at a right angle to the individual's axis of vision anddoes not tilt pupillometer. The headrest 16 can be used to provideoptimum positioning of pupillometer 10 relative to the eye beinganalyzed.

Pupillary measurements can be divided into three phases as shown inFIGS. 4A-4C. Pressing either one of the buttons 14 a (for the rightpupil) or 14 b (for the left pupil) on the keypad 14 can activate thefirst phase, i.e., the targeting phase of pupillometer 10. By pressingkey 14 a, pupillometer 10 automatically saves the data as left eye data,and by pressing key 14 b, pupillometer 10 automatically saves the dataas right eye data. In one embodiment, the operator of pupillometer 10holds down button 14 a or 14 b during the targeting phase while keepingpupillometer 10 snuggly up to the subject's eye. During the targetingphase, a video image of the eye is displayed in the LCD window as shownin FIG. 2 and FIG. 4A. The subject's pupil must be centered within thefield of view as shown in FIGS. 2 and 4A.

During phase 2 of pupillary measurement, pupillometer 10 has a pupilfinder that automatically detects the pupil 20 and marks it with aperimeter 25 drawn around the perimeter of the pupil 20. Algorithms andsoftware for detecting a pupil and drawing a perimeter around it areknown in the art. For example, U.S. Pat. No. 7,147,327, describesvarious imaging processing procedures and methods that can be used to dothat. The perimeter 25 can be any color that is easy to visualize, suchas green, white, red, etc. From the beginning of phase 1 until now, theoperator has been holding down the button 14 a or 14 b.

Once the pupil finder of pupillometer 10 has found the pupil 20 and hasmarked it with the perimeter 25, the operator can now release the button14 a or 14 b. Release of the button 14 a or 14 b initiates the thirdphase, which is the actual measurement phase. In the measurement phase,pupillometer 10 subject's the individual's eye to a flash of lightapplied at time 0.0 seconds. In other words the flash of light isapplied at the same instant as the first image of the pupil is beingrecorded. The flash of light can also be applied just before or justafter the pupillometer begins recording images of the pupil. Asdiscussed above, the intensity and duration of the flash of light can becontrolled by the operator. FIG. 4C shows an image on the display 12 ofpupillometer 10 of the pupil as it is being recorded during themeasurement phase. The pupillometer may also be set to operate withoutthe flash of light, such that measurements are taken of a pupil that hasnot been stimulated but is at rest. When the comparison of the left andright pupil is made for measurements that don't involve a stimulus, thevideos of the right and left pupil are synchronized in the same manneras when measurements are taken after a stimulus.

FIG. 3 shows a screen shot of the display 12 of pupillometer 10 showinga results page that includes various measurements of the pupil that wassubjected to the light stimulus and recorded during phases 1-3 describedabove. The results page can show a plot of the pupil response and can,for example, report the following information:

-   -   ID, the identification code of the subject measured (for example        0 in FIG. 3); which eye was measured (right in the example in        FIG. 3), and the date and time of the measurement. If the        measurement was affected by certain problems during phases 1-3,        the data shown in the results page may be in a special color,        such as red, to indicate that there was a problem. Some examples        of problems that can occur during measurement are excessive eye        blinks or excessive pupillometer motion.    -   The intensity and duration of the light stimulation. In the        example shown in FIG. 3, the light stimulation intensity was 180        micro Watts for a toal duration of 667 milliseconds. The        duration of the light stimulation is also represented by a        colored vertical line superimposed over the pupil plot (0.0        seconds is always the onset of the light stimulation).    -   MAX and MIN represent the diameter of the pupil before the        constriction (MAX=2.8 mm in this example) and just at the peak        of the constriction (MIN=2.2 mm in this example), respectively        in FIG. 3. These measurements are given in millimeters and are        represented by two horizontal gray lines superimposed over the        pupil plot. The variable CON is the percent of the constriction        (MAX−MIN)/MAX as a percent.    -   LAT is the latency and it represents the amount of time it takes        before the onset of pupilary constriction in response to the        light stimulus. It is given in seconds (for example 0.23 seconds        in the FIG. 3) and is represented by a vertical colored line,        different from the color of the light stimulation duration line,        superimposed over the pupil plot.    -   ACV and MCV are the average and the maximum constriction        velocity and they are given in millimeters/second, respectively.        The negative sign differentiates the constriction from the        opposite papillary movement that is dilation. Both velocities        refer to the constricting movement of the pupil diameter        responding to the flash of light.    -   ADV is the dilation velocity (given in millimeters/second) and        represents the average papillary velocity, when, after having        reached the peak of the constriction, the pupil tends to recover        and to dilate back to its initial resting size. Pupillary        recovery after a light reflex constriction is usually        characterized by an initial and more rapid phase followed by a        much slower converging movement. The dilation velocity reported        here refers to the initial and stronger recovery and is        indicated in the graph in FIG. 3 by a line fit to the        corresponding dilation phase of the pupil profile.    -   T75 is the total time taken by the pupil to constrict and then        to return to 75% of the initial resting pupil size. It is given        in seconds and is represented by a vertical colored line        superimposed on the pupil plot in a color that is different than        the other lines that are superimposed on the pupil plot.

The above describes operation of pupillometer 10 with respect to eachmeasurement of a pupil that is taken. When taking a measurement of apupil, the operator uses the keypad 14 to enter various data regardingthe pupil. That data can include, e.g., the identity of the individualwhose pupil it is. As discussed above, pupillometer 10 memory storesthat information and can use it to perform direct comparisons betweenthe response of the left eye and the response of the right eye to theflash of light applied by pupillometer 10. Which pupil of the individualis being measured is specified by the keypad buttons 14 a and 14 b. Ifthe user presses keypad button 14 a then the pupillometer automaticallystores the pupillary measurement as left eye data, and if the userpresses keypad button 14 b then the pupillometer automatically storesthe pupillary measurement data as right eye data.

In one embodiment, pupillometer 10 has the following components thatenable it to perform a comparison between the left and right eyes of theindividual. Pupillometer 10 has a display 12 that is sized tosimultaneously display a video of y or more seconds in length of a leftpupil and a video of y or more seconds in length of a right pupil of thesame individual. The lengths of each video can be anywhere from 1 secondor less to sixty or more minutes. Pupillometer 10 has an imagingapparatus that includes a pupil finder that identifies the perimeter ofa pupil and a microprocessor. The imaging apparatus is capable ofrecording images of an individual's pupils at a rate of x frames persecond for a period of y or more seconds and playing back said images asa video at x frames per second or at another rate that is faster orslower than x frames per second. As explained above, in one embodiment,the imaging apparatus records or samples the images at a rate ofapproximately 30 fps for a period of approximately 3.0 seconds. Theplayback mechanism of pupillometer 10 can play the videos back ondisplay 12 at 30 fps, or at a different rate controlled by the userusing the keypad 14 to control the playback rate. The playback mechanismcan also pause the video playback or it can fast-forward or rewind thevideo playback at various speeds controlled by the user using the keypad14 controls, which can include pause, rewind, fast-forward and videoplayback, fast-forward and rewind speed buttons and/or functions. Forexample, the user can view the images one image set at a time and cancontrol how long he or she wants to view the image set before manuallyforwarding or advancing to the next set of images or rewinding to theprevious set of images. This can be done to compare the right pupil tothe left pupil image set by image by set for each set of images takenduring the procedure. The user can pause as long as he or she wants at aparticular set of images to, for example, compare the difference betweenthe right pupil and the left pupil in that set of images.

Pupillometer 10 also has a memory in communication with themicroprocessor. The memory has stored therein a pupil comparisonprogram. The pupil comparison program can include a pupil finder asdescribed above. The pupil comparison program enables the microprocessorto perform the following functions:

-   -   (i) identify a center of the left pupil and a center of the        right pupil for each image frame;    -   (ii) synchronize each frame of the two videos starting from the        first frame;    -   (iii) cause the display to display the two videos simultaneously        such that each of the frames of the video of the left eye is        synchronized to a corresponding frame of the video of the right        eye when played back on the display;    -   (iv) cause the two videos to be displayed so that the center of        the left pupil in each frame is aligned on the display with the        center of the right pupil for the corresponding frame.

FIG. 5 shows one example of a pupillometer display 12 showing an imageframe 21 of a left pupil 20L recorded during measurement of the pupil asdescribed above, and an image frame 22 of a right pupil 20R recordedduring measurement of the pupil as described above. Image frame 21 ispart of a series of sequential image frames of the left pupil recordedat a rate of x frames per second and which together form a video of yseconds in length. In one embodiment, x is approximately 30 and y isapproximately 3.0. In other embodiments, x can be about 10 (or less),about 20, about 40, about 50 or more and y can be 1, 2, 4, 5 or up to3600 or more, and in general x can be between about 1 (or less) andabout 100 frames (or more) per second, and y can be any length of timebetween about one (1) second and 3600 seconds (i.e., 60 minutes)(ormore). Image frame 22 is part of a series of sequential image frames ofthe right pupil recorded at the same rate of x frames per second andwhich together form a video of y seconds in length, which is the samelength as the video associated with image frame 21.

Thus, in one embodiment, there are approximately 90 image frames for thevideo of the left pupil and 90 image frames for the video of the rightpupil. Each image frame of the video of the left pupil has acorresponding image frame in time in the video of the right pupil. Forexample, image frame 1 of the left pupil and image frame 1 of the rightpupil are both taken at the exact same amount of time after onset of theflash of light from pupillometer 10 (alternatively, image frame 1 can betaken just before or just after onset of the flash of light). Thus,image frame 1 of the left pupil and image frame 1 of the right pupil arecorresponding image frames. Likewise, image frame 2 of the left pupiland image frame 2 of the right pupil are both taken at the exact sameamount of time after onset of the flash of light from pupillometer 10(or from onset of video recording without a flash of light).Alternatively, image frame 2 of each pupil can be taken just before orjust after onset of the flash of light. Thus, image frame 2 of the leftpupil and image frame 2 of the right pupil are corresponding imageframes, and so on and so forth for approximately 90 images that whenplayed back at 30 fps form a video that lasts about 3 seconds. In theexample shown in FIG. 5, image frame 21 is the 24th image of the lefteye taken by pupillometer 10, which means that it is taken at 800milliseconds after onset of the flash of light from pupillometer 10 (orfrom onset of video recording without a flash of light). Likewise, imageframe 22 is the 24^(th) image of the right eye taken by pupillometer 10,which means that it too is taken at 800 milliseconds after onset of theflash of light from pupillometer 10 (or from onset of video recordingwithout a flash of light).

It should be understood that with respect to all embodiments describedherein, the first image of each pupil can be taken just before,simultaneously with, or just after the onset of the flash of light.Thus, for example, the first image of each pupil can be taken withinone, two, three, four, five, six, seven, eight, nine or moremilliseconds up to one second before or after the onset of the flash oflight. It can also be taken simultaneously with the flash of light. Inone embodiment, the first image of each pupil is taken 500 millisecondsbefore the onset of the flash of light.

As shown in FIG. 5, the pupil comparison program enables themicroprocessor to determine the center of each pupil and to draw astraight line 30 that runs through the center of each pupil. That waypupils 20L (left pupil) and 20R (right pupil) are lined up with oneanother on the display. Pupil centering programs are known in the artand some are described in U.S. Pat. No. 7,147,327. FIG. 5 shows just oneframe of each pupillary measurement of the left pupil 20L being lined upwith its corresponding pupillary measurement frame of the right pupil20R, but each frame of the pupillary measurement of the left pupil 20Lis lined up with its corresponding pupillary measurement frame of theright pupil on the display 12. Thus, when the two videos are played backon the display 12 simultaneously, it is easy to see the difference inresponse of the left pupil relative to the right pupil. One of thereasons why it is so important to align and center the two pupils in thevideo playback mode is to compensate for eye movement so that theoperator can easily compare one eye to the other.

The pupil comparison program provides another feature that makes it eveneasier to follow the difference in the pupillary responses of the leftand right pupil. The pupil comparison program enables the microprocessorto draw a pair of parallel straight lines that extend from the perimeterof the left pupil to the perimeter of the right pupil in each imageframe. As shown in FIG. 5, the parallel lines have a first section32L/31L and a second section 32R/31R, wherein in the first section32L/31L the distance between the parallel lines is defined by thediameter of the left pupil 20L for each frame, and in the second sectionthe distance between the parallel lines 32R/31R is defined by thediameter of the right pupil 20R for each frame. The diameter of the leftpupil 20L is defined by the pupil perimeter 25L, which is established bypupillometer 10 using its pupil finder. The diameter of the right pupil20R is defined by the pupil perimeter 25R, which is likewise establishedby pupillometer 10 using its pupil finder. In order to further make iteasier to visualize the difference in response between the left andright eyes, the first section lines 32L/31L can be a different colorthan the second section lines 32R/31R. For examples parallel lines32L/31L can be red while parallel lines 32R/31R can be green.

FIG. 6 shows the 72^(nd) image frame of each video of each eye, whichmeans that each frame was taken at 2.4 seconds after onset of the flashof light of pupillometer 10. At 2.4 seconds after onset of the flash oflight, the pupils 20L and 20R have dilated back to their restingposition. Looking at the still images in FIGS. 5 and 6, it would appearthat there is very little pupil size asymmetricity in this individual.But for a better understanding, one would view the video comparing thetwo sets of images at 30 fps or perhaps at a slower speed such as 10 fpsto get a much clearer view of whether or not there is substantialanisocoria or asymmetry in pupillary response to light stimulus. Thepairing of parallel lines 32L/31L with 32R/31R makes it very clearwhether there is anisocoria or asymmetry in papillary response to lightstimulus.

FIGS. 7-8 show a further feature of pupillometer 10. This furtherfeature allows the user to see on the display 12 of pupillometer 10 notjust synchronized and centered videos of the left and right pupil at thesame time, as described above, but to view a graphical representation ofthe pupillary response of the left and right pupils superimposedtogether on a single graph. Images in FIG. 7 are taken at about 600milliseconds after onset of the flash of light from pupillometer 10 (orfrom onset of video recording without a flash of light) as the pupils20L and 20R are dilating. There is some minor difference as depicted inthe graph below the images of the pupils 20L and 20R and as shown by thedisconnection between sections 32L/31L and 32R/31R of the parallellines. Images in FIG. 8 are taken at about 1.5 seconds after onset ofthe flash of light from pupillometer 10 (or from onset of videorecording without a flash of light) as the pupils 20L and 20R arerecovering back to their resting state. There is again some minordifference as depicted in the graph below the images of the pupils 20Land 20R and as shown by the disconnection between sections 32L/31L and32R/31R of the parallel lines. Images in FIG. 9 are taken at about 2.6seconds after onset of the flash of light from pupillometer 10 (or fromonset of video recording without a flash of light) as the pupils 20L and20R have fully dilated back to their resting position. Again, there issome minor difference as depicted in the graph below the images of thepupils 20L and 20R and as shown by the disconnection between sections32L/31L and 32R/31R of the parallel lines. If viewed in rapid successionat 30 fps or even if slowed down to 10 fps, the operator of pupillometer10 would be able to clearly see the difference in pupillary responsebetween the left and right pupils to the flash of light frompupillometer 10 (or from onset of video recording without a flash oflight). For example, the user can view the images one image set at atime and can control how long he or she wants to view the image setbefore manually forwarding or advancing to the next set of images orrewinding to the previous set of images. This can be done to compare theright pupil to the left pupil image set by image by set for each set ofimages taken during the procedure. The user can pause as long as he orshe wants at a particular set of images to, for example, compare thedifference between the right pupil and the left pupil in that set ofimages.

Methods for monitoring asymmetry in response between the left and righteye are also described herein. The methods are directed to whether ornot an individual has either anisocoria and the level and severity ofanisocoria, or asymmetry in response between the left and right eye to astimulus, such as a light stimulus or other stimulus (or no stimulus atall). Determining whether a patient has anisocoria or asymmetry inresponse can have diagnostic value.

In one aspect, a method for monitoring asymmetry in response to astimulus between a left pupil and a right pupil of an individualinvolves the following steps, which can be performed with the aid ofpupillometer 10 described above and illustrated in FIG. 1, or otherdiagnostic equipment. An operator, usually a medical professional, willposition pupillometer 10 with the headrest 16 against the patient's facearound her left eye with the body of pupillometer 10 being perpendicularrelative to the patient's axis of vision as shown in FIG. 2. It does notmatter which eye is analyzed first as long as the data regarding whetherthe pupillary measurement is of the left eye or right eye is enteredprior to taking the pupillary measurement. Pupillometer 10 is activatedas described and it is used to record for a period of time y at a rateof x image frames per second a response of the left pupil to a flash oflight (or simply recording the pupil at rest without a flash of light).When the measurement phase is activated, pupillometer 10 will issue aflash of light in the field of view of the left eye (or simply recordingthe pupil at rest without a flash of light) and will simultaneouslybegin recording images of the left pupil for a period of time y at arate of x image frames per second as noted above. Recording willautomatically stop after the period of time y has elapsed, and theimages will be stored in the memory of pupillometer 10. The result ofthe recording is a video made up of a number of sequential image framesthat when played back depict in a movie format the response of the pupilto the flash of light (or simply recording the pupil at rest without aflash of light). The same steps are then performed on the right eye andthe image data of the right eye is also stored in the memory ofpupillometer 10.

Now the operator can use the pupil comparison feature of pupillometer 10to display on the display screen 12 of pupillometer 10 simultaneouslythe first set of image frames of the response of the left pupil and thesecond set of image frames of the response of the right pupil to theflash of light (or no stimulus at all). This will initiate the playbackfeature on the pupillometer 10. The pupil comparison feature of thepupillometer 10 will arrange the two sets of image frames on the displayso that the center of the left pupil is aligned with the center of theright pupil on the display and the two sets of image frames aresynchronized per frame starting from the first frame for each set with astraight line running from the center of both pupils. Stated somewhatdifferently, the two videos, the video of the left pupil and the videoof the right pupil, will be aligned on the display 12 so that the centerof the left pupil is aligned with the center of the right pupil on thedisplay 12 and pupillometer 10 will then play the two videossimultaneously and in a synchronized fashion on the display screen 12.

To further enhance the ability of the operator to perceive anyanisocoria, the comparison feature of pupillometer 10 draws a pair ofparallel straight lines that extend from the perimeter of the left pupilto the perimeter of the right pupil in each image frame. The parallellines have a first section and a second section, wherein in the firstsection the distance between the parallel lines is defined by thediameter of the left pupil for each image frame, and in the secondsection the distance between the parallel lines is defined by thediameter of the right pupil for each image frame. The color of theparallel lines in the first section can be different than the color ofthe parallel lines in the second section to make it easier for theoperator to perceive any anisocoria. For example, the parallel lines inthe first section can be green and the parallel lines in the secondsection can be red or vice versa. In addition, the user can view theimages one image set at a time and can control how long he or she wantsto view the image set before manually forwarding or advancing to thenext set of images or rewinding to the previous set of images. This canbe done to compare the right pupil to the left pupil image set by imageby set for each set of images taken during the procedure. The user canpause as long as he or she wants at a particular set of images to, forexample, compare the difference between the right pupil and the leftpupil in that set of images.

In another embodiment, pupillometer 10 can be binocular (not shown) sothat measurements of the left and right eye are taken simultaneously.Binocular Pupillometers, such as Neuroptics'® DP-1000 Pupillometer forResearch are well known in the art.

While the invention is susceptible to various modifications andalternative forms, specific examples thereof have been shown by way ofexample in the drawings and are herein described in detail. It should beunderstood, however, that the invention is not to be limited to theparticular forms or methods disclosed, but to the contrary, theinvention is to cover all modifications, equivalents, and alternativesfalling within the spirit and scope of the appended claims.

We claim:
 1. A method of assessing a health condition of a mammaliansubject comprising: recording images of a response of a left pupil ofthe subject to a stimulus thereby resulting in a first set of sequentialimages; recording images of a response of a right pupil of said subjectto the same stimulus at the same time as the first images were recorded,thereby resulting in a second set of sequential images; displaying on adisplay of a pupilometer simultaneously the first set of images and thesecond set of images, wherein the two sets of images are synchronized,and wherein a center of the left pupil of each image from the first setof sequential images is aligned with a center of the right pupil fromthe second set of sequential images on the display; using thepupilometer to detect anisocoria in the pupillary response of thesubject; and diagnosing the patient with an abnormal health condition inthe presence of anisocoria.
 2. The method of claim 1, wherein themammalian subject is a human.
 3. The method of claim 1, wherein thedisplay generates a pair of parallel lines that extend form theperimeter of the left pupil to the perimeter of the right pupil in eachimage, the parallel lines having a first section and a second section,wherein in the first section the distance between the parallel lines isdefined by the diameter of the left pupil for each image and in thesecond section the distance between the parallel lines is defined by thediameter of the right pupil for each image.
 4. The method of claim 3,wherein the color of the parallel lines in the first section isdifferent from the color of the parallel lines in the second section. 5.The method of claim 3, wherein anisocoria is detected by the differencebetween the sizes of the two pupils as demonstrated by the difference inthe distances between the parallel lines in the first section and of theparallel lines in the second section.